Methods and systems for treating acute heart failure by neuromodulation

ABSTRACT

Methods of treating acute heart failure in a patient in need thereof. Methods include inserting a therapy delivery device into a pulmonary artery of the patient and applying a therapy signal to autonomic cardiopulmonary fibers surrounding the pulmonary artery. The therapy signal affects heart contractility more than heart rate. Specifically, the application of the therapy signal increases heart contractility and treats the acute heart failure in the patient. The therapy signal can include electrical or chemical modulation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/654,525, filed on Oct. 18, 2012 and issued as U.S. Pat. No. 8,798,738on Aug. 5, 2014, which is a continuation of U.S. application Ser. No.12/185,473, filed on Aug. 4, 2008 and issued as U.S. Pat. No. 8,818,501on Aug. 26, 2014, which is a continuation of U.S. application Ser. No.11/951,285, filed on Dec. 5, 2007, which claims priority to U.S.Provisional Application No. 60/873,021, filed on Dec. 6, 2006, each ofU.S. application Ser. No. 12/185,473, U.S. application Ser. No.11/951,285, and U.S. Provisional Application No. 60/873,021 beingincorporated by reference in its entirety herein. The presentapplication is also related to U.S. application Ser. No. 11/222,766,filed on Sep. 12, 2005, which is incorporated by reference herein.

FIELD OF THE INVENTION

The present invention relates to methods and systems for treating acuteheart failure by electrically modulating autonomic cardiopulmonaryfibers.

BACKGROUND OF THE INVENTION

Diseases or injuries causing or resulting in acute heart failure arewidespread. The goals of therapy in acute heart failure are often tocorrect the hemodynamic instability and address decompensation in orderto increase patient mortality. One treatment option for acute heartfailure is the administration of inotropic agents, such as dopamine anddobutamine. However, inotropic agents have both chronotropic andinotropic effects and characteristically increase heart contractility atthe expense of significant increments in oxygen consumption secondary toelevations in heart rate. As a result, although these inotropic agentsincrease myocardial contractility and improve hemodynamics, clinicaltrials have consistently demonstrated excess mortality caused by cardiacarrhythmias and increase in the myocardium consumption.

As such, there is a need for a method of selectively and locallytreating acute heart failure and otherwise achieving hemodynamic controlwithout causing untoward systemic effect.

SUMMARY OF THE INVENTION

The present invention provides methods for treating medical conditionsby transvascular neuromodulation of a target site of an autonomicnervous system. The methods of the present invention for treatingmedical conditions encompass neuromodulation of any combination of oneor more target sites of the autonomic nervous system. Non-limitingexamples of medical conditions that can be treated according to thepresent invention include cardiovascular medical conditions.

In an embodiment, the present invention provides a method of treatingacute heart failure in a patient in need thereof comprising inserting adelivery device into a pulmonary artery and positioning the deliverydevice at a pulmonary trunk of the pulmonary artery. The method alsocomprises applying a therapy signal to at least one sympatheticcardiopulmonary fiber surrounding the pulmonary trunk to treat the acuteheart failure. The at least one sympathetic cardiopulmonary fiberaffects heart contractility more than heart rate.

In another embodiment, the present invention provides a system fortreating acute heart failure comprising a delivery device forpositioning in the pulmonary artery at the pulmonary trunk. The systemfurther includes a controller in communication with the delivery devicefor enabling the delivery device to apply a therapy signal to at leastone sympathetic cardiopulmonary fiber surrounding the pulmonary trunk totreat acute heart failure. The at least one sympathetic cardiopulmonaryfiber affects heart contractility more than heart rate.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of the heart and surrounding areas,showing the stimulation sites according to the present invention.

FIG. 2 is a schematic illustration of the specific nerves wherestimulation can be applied according to an embodiment of the presentinvention.

FIG. 3 is an electrical delivery device to be positioned within thepulmonary artery according to an embodiment of the present invention.

FIG. 4 is a schematic illustration of the components used in acontroller of an embodiment of a system of the present invention.

FIG. 5 is a block diagram of an algorithm to determine action taken by acontroller microprocessor in response to sensor input according to anembodiment of a system of the present invention.

FIG. 6 is a graph showing the peak and average contractility percentagechanges in dogs treated with electrical modulation according to anembodiment of the present invention and as described in Example 1.

FIG. 7 is a graph showing the average percentage change in contractilitycompared to heart rate in dogs treated with electrical modulationaccording to an embodiment of the present invention and as described inExample 1.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides methods for treating medical conditionsby transvascular neuromodulation of a target site of an autonomicnervous system. The methods of the present invention for treatingmedical conditions encompass neuromodulation of any combination of oneor more target sites of the autonomic nervous system. Non-limitingexamples of medical conditions that can be treated according to thepresent invention include cardiovascular medical conditions.

With respect to treating cardiovascular medical conditions, such medicalconditions can involve any medical conditions related to the componentsof the cardiovascular system such as, for example, the heart and aorta.Non-limiting examples of cardiovascular conditions includepost-infarction rehabilitation, shock (hypovolemic, septic, neurogenic),valvular disease, heart failure, angina, microvascular ischemia,myocardial contractility disorder, cardiomyopathy, hypertensionincluding pulmonary hypertension and systemic hypertension, orthopnea,dyspenea, orthostatic hypotension, dysautonomia, syncope, vasovagalreflex, carotid sinus hypersensitivity, pericardial effusion, heartfailure, and cardiac structural abnormalities such as septal defects andwall aneurysms. Non-limiting examples of vessels into which therapydelivery devices, according to the present invention, are positioned toaccess autonomic target sites innervating components of thecardiovascular system are the carotid arteries; aorta; superior venacava; inferior vena cava; pulmonary veins and arteries; carotidarteries; and subclavian arteries and veins. In a preferred embodiment,a therapy delivery device is used in conjunction with a pulmonary arterycatheter, such as a Swan-Ganz type pulmonary artery catheter to deliverytransvascular neuromodulation via the pulmonary artery to an autonomictarget site to treat a cardiovascular condition according to the presentinvention. Specifically, in this preferred embodiment, a therapydelivery device is housed within one of the multiple vessels of apulmonary artery catheter.

The present invention provides systems and methods for treating acuteheart failure, also known as decompensated heart failure, by modulatingat least one sympathetic cardiopulmonary fiber that affects heartcontractility more than heart rate. In a preferred embodiment, aplurality of sympathetic cardiopulmonary fibers is modulated thatcollectively affect heart contractility more than heart rate. The fiberscan be modulated by chemical and/or electrical modulation (includingablation) and the modulation includes stimulating and/or inhibiting thefibers. In the case of chemical modulation, bioactive agents may beused, including neurotransmitter mimics; neuropeptides; hormones;pro-hormones; antagonists, agonists, reuptake inhibitors, or degradingenzymes thereof, peptides; proteins; therapeutic agents; amino acids;nucleic acids; stem cells, or any combination thereof and may bedelivered by a slow release matrix or drug pump.

According to the methods of the present invention, a delivery device,which can be an electrode in the case of electrical modulation, or adrug delivery device (e.g., a catheter) in the case of chemicalmodulation, is inserted into the pulmonary artery and positioned at alocation within the pulmonary trunk such that activation of the deliverydevice at that location results in selective modulation of sympatheticcardiopulmonary fibers. Specifically, the sympathetic cardiopulmonaryfibers that are modulated collectively affect heart contractility morethan heart rate. Preferably, the delivery device is positioned at a sitewithin the pulmonary artery such that activation of the delivery deviceresults in the greatest effect on heart contractility and the leasteffect on heart rate and/or oxygen consumption compared to activation ofthe delivery device at any other site in the pulmonary artery. Incertain embodiments, the effect on heart contractility is to increaseheart contractility. In certain embodiments, electrical modulation isprovided in combination with chemical modulation. In such embodiments,the present invention also provides systems that include electrical andchemical delivery devices.

FIG. 1 is a schematic illustration of the heart 10 and the pulmonaryartery 20. As is known in the art, the pulmonary artery includes thepulmonary trunk 30, which begins at the base of the right ventricle; theright pulmonary artery 40; and the left pulmonary artery 50. Thepulmonary trunk is short and wide, approximately 5 cm (2 inches) inlength and 3 cm (1.2 inches) in diameter. In a preferred embodiment, anelectrical delivery device is activated at the site 60 of the pulmonarytrunk 30 that is at the base of the T-shape (circled in FIG. 1) formedby the left branch and right branch of the pulmonary artery.

The neuromodulation of the present invention is accomplished by applyinga therapy signal, such as an electrical and/or chemical signal to thepulmonary trunk, such as at least one of the anterior wall, theposterior wall, the superior wall, and the lateral wall. The therapysignal is thereby applied to the sympathetic cardiopulmonary fibers, ornerves, surrounding the pulmonary trunk. These sympathetic fibers caninclude the right sympathetic cardiopulmonary nerves and the leftsympathetic cardiopulmonary nerves, as illustrated in FIG. 2. The rightsympathetic cardiopulmonary nerves include the right dorsal medialcardiopulmonary nerve 110 and the right dorsal lateral cardiopulmonarynerve 112. The left sympathetic cardiopulmonary nerves include the leftventral cardiopulmonary nerve 114, the left dorsal medialcardiopulmonary nerve 116, the left dorsal lateral cardiopulmonary nerve118, and the left stellate cardiopulmonary nerve 200.

The delivery device can be introduced by any route or means to accessthe pulmonary artery. For example, the delivery device can be introducedthrough a large vein, such as the internal jugular, subclavian, orfemoral veins or an artery and can be threaded, perhaps with the aid offluoroscopy, into the pulmonary artery and placed at the pulmonarytrunk.

The present invention also provides systems for treating acute heartfailure. In an embodiment, the system includes a delivery device, whichcan be an electrical and/or chemical delivery device (such as anelectrode and/or catheter) for positioning in the pulmonary artery atthe pulmonary trunk and a controller, such as a pulse generator when anelectrical delivery device is used and a drug pump when a chemicaldelivery device is used, in communication with the delivery device forenabling the delivery device to apply a therapy signal to at least onesympathetic cardiopulmonary fiber surrounding the pulmonary trunk totreat acute heart failure, wherein said at least one sympatheticcardiopulmonary fiber affects heart contractility more than heart rate.In certain embodiments, the system further includes a sensor formeasuring cardiac parameters and generating a sensor signal.

FIG. 3 provides an illustration of an exemplary electrical deliverydevice that can be used in accordance with an embodiment of a system ofthe present invention when electrical modulation is desired. Theelectrical delivery device is an intraluminal electrode assembly 230that can provide intimate contact with a vessel wall. The intraluminalelectrode assembly 230 includes a plurality of insulated electricalconductors 236, each conductor 236 connected to a preferably cylindricalelectrode 232 disposed annularly thereon. There can be any number ofconductors 236 having any number of electrodes 232 disposed thereon, butin a preferred embodiment, there are eight conductors with eachconductor have one electrode disposed thereon. A frame 234 is connectedto the ends of the plurality of insulated electrical conductors 236. Incertain embodiments, electrodes 232 serve as cathodes and frame 234serves as an anode.

Frame 234 is collapsible for fitting within a catheter lumen 240 duringinsertion into the body. Specifically, frame 234 has a first collapsedconfiguration smaller than the diameter of lumen 240 and, when deployed,a second radially expanded configuration designed to contact the vesselwall against which intraluminal electrode assembly 230 is positioned.Frame 234 is preferably fabricated from a super-elastic material, suchas nitinol, for example, which allows frame 234 to return to itsexpanded state when deployed from lumen 240 and assume a collapsed statewhen retracted back into lumen 240. In a preferred embodiment, thedistal end of frame 234 has an open stent-like configuration, preferablya plurality of diamond shapes 238 connected to each other by connector242, creating a closed circular loop. Although electrodes 232 can bemounted at any position on insulated conductor 236, they are preferablymounted near frame 234.

In a preferred embodiment, lumen 240 is one lumen of a multi-lumenpulmonary catheter as described in more detail in co-pending applicationSer. No. 11/222,774, filed on Sep. 12, 2005.

Electrical delivery device 230 is connected via a stimulationlead/catheter to a controller (not shown). The electrical deliverydevice may be placed temporarily in the pulmonary trunk adjacent to asympathetic cardiopulmonary fiber. The controller of an embodiment of asystem of the present invention is used to operate and supply power tothe delivery device and enable the delivery device to deliver a therapysignal to a sympathetic cardiopulmonary fiber. The controller may bepowered by a battery (which can be rechargeable), an external powersupply, or a fuel cell. The controller may also be integral with thedelivery device (such as a single stimulation lead/power generator or asingle catheter/drug delivery pump). In the case of electricalmodulation, the controller may change the output to the electrode by wayof polarity, pulse width, amplitude, frequency, voltage, current,intensity, duration, wavelength, and/or waveform. The controller mayoperate any number or combination of electrodes. In the case of chemicalmodulation, the controller may change the dosage, timing or otherparameters of drug delivery. The controller may operate any number ofcombination of drug ports. The controller can be external to thepatient's body for use by the attending physician to program thecontroller and to monitor its performance or internal to the patient'sbody.

In the case of electrical modulation, the controller activates theelectrical delivery device to initiate or adjust application of anelectrical signal including terminating, increasing, decreasing, orchanging the rate or pattern of a pulsing parameter. The controller alsoenables an electrical delivery device to deliver an electrical signalthat may be episodic, continuous, phasic, in clusters, intermittent,upon demand by the patient or medical personnel, or preprogrammed torespond to a sensor. Preferably, the oscillating electrical signal isoperated at a voltage between about 0.1 microvolts to about 20 V. Morepreferably, the oscillating electrical signal is operated at a voltagebetween about 1 V to about 15 V. For microstimulation, it is preferableto stimulate within the range of 0.1 microvolts to about 1 V.Preferably, the electric signal source is operated at a frequency rangebetween about 2 Hz to about 2500 Hz. More preferably, the electricsignal source is operated at a frequency range between about 2 Hz toabout 200 Hz. Preferably, the pulse width of the oscillating electricalsignal is between about 10 microseconds to about 1,000 microseconds.More preferably, the pulse width of the oscillating electrical signal isbetween about 50 microseconds to about 500 microseconds. Preferably, theapplication of the oscillating electrical signal is: monopolar when theelectrode is monopolar; bipolar when the electrode is bipolar; andmultipolar when the electrode is multipolar. The waveform may be, forexample, biphasic square wave, sine wave, or other electrically safe andfeasible combinations. The electrical signal may be applied to multipletarget sites simultaneously or sequentially.

In the case of chemical modulation, the controller can enable a drugport to deliver a bioactive agent to the target site. Where chemical andelectrical modulation are both used, the controller can also coordinatedelivery of the bioactive agent with the electrical neuromodulation(e.g., delivery of the bioactive agent prior to, concurrent with, orsubsequent to electrical neuromodulation). The delivery of the bioactiveagent maybe continuous, intermittent, chronic, phasic, or episodic.

An open-loop or closed-loop feedback mechanism may be used inconjunction with any of the methods of the present invention. In anopen-loop feedback mechanism, a professional can monitor cardiacparameters of the patient and accordingly adjust the therapy signalapplied to sympathetic cardiopulmonary fiber. Non-limiting examples ofcardiac parameters monitored include arterial blood pressure, centralvenous pressure, capillary pressure, systolic pressure variation,arterial blood gases, cardiac output, systemic vascular resistance,pulmonary artery wedge pressure, and mixed venous oxygen saturation.Cardiac parameters can be monitored by an electrocardiogram, invasivehemodynamics, an echocardiogram, or blood pressure measurement or otherdevices known in the art to measure cardiac function. Other parameterssuch as body temperature and respiratory rate can also be monitored andprocessed as part of the feedback mechanism.

In a closed-loop feedback mechanism, the cardiac parameters areprocessed by at least one sensor and the neuromodulation is continuouslyadjusted according to the output generated by the sensor. Specifically,a sensor detects a cardiac parameter and generates a sensor signal. Thesensor signal is processed by a sensor signal processor that provides acontrol signal to a signal generator. The signal generator, in turn,generates a response to the control signal by activating or adjustingthe therapy signal applied by the delivery device to a sympatheticcardiopulmonary fiber. The control signal may be an indication toinitiate, terminate, increase, decrease or change the rate or pattern ofa pulsing or dosing parameter of the neuromodulation and the response tothe control signal can be the respective initiation, termination,increase, decrease or change in rate or pattern of the respectivepulsing or dosing parameter. The processing of closed-loop feedbacksystems for electrical neuromodulation is described in more detail inrespective U.S. Pat. Nos. 6,058,331 and 5,711,316, both of which areincorporated by reference herein.

Closed-loop electrical modulation, according to the present inventioncan be achieved by a modified form of an implantable SOLETRA, KINETRA,RESTORE, or SYNERGY signal generator available from Medtronic,Minneapolis, Minn. as disclosed in U.S. Pat. No. 6,353,762, the teachingof which is incorporated herein in its entirety, a controller asdescribed in FIG. 4, or utilization of CIO DAS 08 and CIO-DAC 16 Iprocessing boards and an IBM compatible computer available fromMeasurement Computing, Middleboro, Mass. with Visual Basic software forprogramming of algorithms. Such controllers can be modified forexternal, as opposed to implantable use. With reference to FIG. 4, anillustration of a non-limiting example of a controller comprising amicroprocessor 76 such as an MSP430 microprocessor from TexasInstruments Technology, analog to digital converter 82 such as AD7714from Analog Devices Corp., pulse generator 84 such as CD1877 from HarrisCorporation, pulse width control 86, lead driver 90, digital to analogconverter 88 such as MAX538 from Maxim Corporation, power supply 72,memory 74, and communications port or telemetry chip 70 are shown.Optionally, a digital signal processor 92 is used for signalconditioning and filtering. Input leads 78 and 80 and output leads 91and 93 are also illustrated. Additional stimulation leads, sensors, andchemical delivery devices may be added to the controller as required. Asa non-limiting example, inputs from sensors, such as a pulmonary arterywedge pressure sensor, are input to analog to digital converter 82.Microprocessor 76 receiving the sensor inputs uses algorithms to analyzethe cardiac parameter of the patient and using PID, Fuzzy logic, orother algorithms, computes an output to pulse generator drivers 90 and94, respectively, to neuromodulate the target site where the deliverydevices are placed. The output of analog to digital converter 82 isconnected to microprocessor 76 through a peripheral bus includingaddress, data and control lines. Microprocessor 76 processes the sensordata in different ways depending on the type of transducer in use. Whenthe signal on the sensor indicates a cardiac parameter outside ofthreshold values, for example reduced pulmonary artery wedge pressure,programmed by the clinician and stored in a memory, the therapy signalapplied through output drivers 90 and 94 of the controller will beadjusted. The output voltage or current from the controller are thengenerated in an appropriately configured form (voltage, current,frequency), and applied to the one or more delivery devices placed atthe target site for a prescribed time period to elevated the pulmonaryartery wedge pressure. If the patient's pulmonary artery wedge pressureas monitored by the system is not outside of the normal thresholdlimits, or if the controller output (after it has timed out) hasresulted in a correction of the pulmonary artery wedge pressure towithin a predetermined threshold range, no further therapy signal isapplied to the target site and the controller continues to monitor thepatient via the sensors. A block diagram of an algorithm which may beused in the present invention is shown in FIG. 3.

Referring to FIG. 5, suitably conditioned and converted sensor data 98can be input to the algorithm in block 100. The program can compute atleast one value of at least one cardiac parameter such as, for examplepulmonary artery wedge pressure or cardiac output, and compares themeasured value of the cardiac parameter to a pre-determined range ofvalues, which is determined in advance to be the desired therapeuticrange of values. This range can be programmed into the microprocessorvia the telemetry or communications port of the controller. Thealgorithm can compare 110, and then can determine whether or not themeasured value lies outside the pre-determined range of values 120. Ifthe measured cardiac parameter value is not outside the pre-determinedrange of values, the program can continue to monitor the sensors andreiterates the comparison part of the algorithm. If the measured cardiacparameter value is outside of the pre-determined range of values, adetermination or comparison can be made 130, as to whether the value istoo high or too low compared with the pre-determined range. If thecardiac parameter value is too high, an adjustment to the deliverydevice can be made 150, to lower the cardiac parameter value of thepatient by calculating an output signal for the pulse generator or drugdelivery device to deliver a sufficient amount of the pharmaceutical orelectrical modulation to lower the cardiac parameter of the patient. Thealgorithm can continue to monitor the cardiac parameter following theadjustment. If the cardiac parameter value is too low then an adjustmentto the delivery device can be made 140, to raise the cardiac parametervalue by calculating an output signal for the pulse generator or drugdelivery device to deliver a sufficient amount of a pharmaceutical orelectrical modulation to raise the cardiac parameter value of thepatient. The algorithm can continue to monitor the cardiac parameter ofthe patient 100, following the adjustment. The amount of adjustment mademay be determined by proportional integral derivative algorithms of byimplementation of Fuzzy logic rules. Of course, the above-describedsensory system is just exemplary and other ways of processing sensorydata can be utilized.

With respect to the control of specific electrical parameters, thestimulus pulse frequency may be controlled by programming a value to aprogrammable frequency generator using the bus of the controller. Theprogrammable frequency generator can provide an interrupt signal to themicroprocessor through an interrupt line when each stimulus pulse is tobe generated. The frequency generator may be implemented by modelCDP1878 sold by Harris Corporation. The amplitude for each stimuluspulse may be programmed to a digital to analog converter using thecontroller's bus. The analog output can be conveyed through a conductorto an output driver circuit to control stimulus amplitude. Themicroprocessor of the controller may also program a pulse width controlmodule using the bus. The pulse width control can provide an enablingpulse of duration equal to the pulse width via a conductor. Pulses withthe selected characteristics can then be delivered from signal generatorthrough a cable and lead to the target site or to a device such as aproportional valve or pump. The microprocessor can execute an algorithmto provide modulation of a target site with closed loop feedbackcontrol. For some types of sensors, a microprocessor and analog todigital converter will not be necessary. The output from sensor can befiltered by an appropriate electronic filter in order to provide acontrol signal for signal generator. An example of such a filter isfound in U.S. Pat. No. 5,259,387 “Muscle Artifact Filter,” issued toVictor de Pinto on Nov. 9, 1993, incorporated herein by reference in itsentirety. Of course, the specific electrical and/or chemical parameterscan be controlled in other ways as well.

EXAMPLES Example 1

Six open-chest dogs were instrumented with a left ventricle conductancecatheter and an aortic flow probe. Modified electrode-catheters wereplaced inside the pulmonary artery under echocardiographic andfluoroscopic guidance in five dogs. In the last dog, a stent-basedelectrode, as illustrated in FIG. 3, was used. Stimulation was appliedat 20 Hz, 0.4 ms, and 15-25 mA. The corresponding hemodynamic effectsare reported as averages of 30 second periods of continuous recording.

Pressure variation in the left ventricle over time increased in alldogs. The average increment was 25.7% (+/−11.8) and the average ofmaximum increase variation was 28.3 (+/−8.9). Emax was measured in thelast animal, showing a 45% increase. The average reduction of RRinterval during stimulation was 3.3% (+/−10.4).

Therefore, electrical modulation via a pulmonary artery catheter canproduce positive inotropic effects with minimal changes in heart rate.

Example 2

Eight open-chest dogs are instrumented with a left ventricle conductancecatheter and an aortic flow probe. Modified electrode-catheters areplaced inside the pulmonary artery under echocardiographic andfluoroscopic guidance in five dogs. In three dogs, a stent-basedelectrode, as illustrated in FIG. 3, is used. Stimulation is applied at20 Hz, 0.4 ms, and 15-25 mA. The corresponding hemodynamic effects arereported as averages of 30 second periods of continuous recording.

FIG. 6 shows the percentage changes in dP/dt max for each dog whencompared to the baseline. Specifically, FIG. 6 shows the peak dP/dt max% change achieved during modulation and the average % change in dP/dtmax in a period of 30 seconds. There is significant increase in dP/dtmax during modulation ranging from 21-22 to 44-45%. However, there is nosignificant change between the average and the peak value.

FIG. 7 compares the average dP/dt max to the percentage increase inheart rate in the eight dogs. As shown, the heart rate increase isminimal when compared to increase in heart contractility (dP/dt max).

The foregoing description and examples has been set forth merely toillustrate the invention and are not intended as being limiting. Each ofthe disclosed aspects and embodiments of the present invention may beconsidered individually or in combination with other aspects,embodiments, and variations of the invention. In addition, unlessotherwise specified, none of the steps of the methods of the presentinvention are confined to any particular order of performance.Modifications of the disclosed embodiments incorporating the spirit andsubstance of the invention may occur to persons skilled in the art andsuch modifications are within the scope of the present invention.Furthermore, all references cited herein are incorporated by referencein their entirety.

The invention claimed is:
 1. A therapy delivery device for treatingcardiovascular medical conditions, comprising: a plurality of insulatedelectrical conductors each having a distal end; a plurality ofelectrodes, each said electrode of the plurality of electrodes being inelectrical communication with one said insulated electrical conductor ofplurality of insulated electrical conductors; a collapsible frameconnected to the distal ends of the plurality of insulated electricalconductors, the collapsible frame defining a closed circular loop joinedby a plurality of connectors, the plurality of electrodes proximal tothe collapsible frame; the collapsible frame configured to expand from afirst position when positioned within a catheter lumen to a secondposition when positioned outside the catheter lumen and collapses backto the first position within the catheter lumen when retracted back intothe catheter lumen, where in use the plurality of electrodes areconfigured to substantially contact one or more portions of a pulmonaryartery of a subject and to deliver a therapy signal to at least oneautonomic fiber in proximity to the pulmonary artery to affect one ormore of cardiac output and hemodynamics, wherein the therapy signal can,when in use, both increase heart contractility and affect heartcontractility more than heart rate; a controller in electricalcommunication with one or more of the plurality of conductors andplurality of electrodes; and one or more sensors for measuringbiological parameters and generating one or more sensor signals, the oneor more sensors operationally connected to the controller, wherein thebiological parameters comprise one or more of arterial blood pressure,central venous pressure, capillary pressure, systolic pressurevariation, arterial blood gases, cardiac output, systemic vascularresistance, pulmonary artery wedge pressure, and mixed venous oxygensaturation, wherein the controller adjusts the therapy signal deliveredby the therapy delivery device in response to the one or more sensorsignals.
 2. The device of claim 1, wherein the plurality of electrodesserve as cathodes and the collapsible frame serves as an anode.
 3. Thedevice of claim 1, wherein the collapsible frame comprises asuperelastic material.
 4. The device of claim 3, wherein thesuperelastic material comprises nitinol.
 5. The device of claim 1,wherein the frame comprises an open stent-like configuration at a distalend.
 6. The device of claim 5, wherein the configuration comprisesdiamond shapes connected to each other the connectors, sufficient tocreate the closed circular loop.
 7. The device of claim 1, wherein theframe is capable of delivering a bioactive agent prior to, concurrentwith or subsequent to electrical modulation.
 8. The device of claim 7,where the controller operates one or more drug ports for delivery ofbioactive agents.
 9. The device of claim 1, wherein the at least oneautonomic fiber comprises at least one of sympathetic fibers andparasympathetic fibers.
 10. The device of claim 9, wherein thesympathetic fibers comprise one or more of right sympathetic nerves andleft sympathetic nerves.
 11. The device of claim 10, wherein the rightsympathetic nerves comprise one or more of right dorsal medialcardiopulmonary nerves and right dorsal lateral cardiopulmonary nerves.12. The device of claim 10, wherein the left sympathetic nerves compriseone or more of left ventral cardiopulmonary nerves, left dorsal medialcardiopulmonary nerves, left dorsal lateral cardiopulmonary nerves andleft stellate cardiopulmonary nerves.
 13. The device of claim 1, whereineach of the plurality of electrodes is annularly disposed on one of theplurality of insulated electrical conductors.
 14. A therapy deliverydevice for treating cardiovascular medical conditions, the therapydelivery device comprising: a plurality of insulated electricalconductors each having a distal end; a plurality of electrodes, eachsaid electrode of the plurality of electrodes being in electricalcommunication with one said insulated electrical conductor of theplurality of insulated electrical conductors, the plurality ofelectrodes being configured to contact one or more portions of apulmonary artery of a subject and configured to deliver a therapy signalto at least one autonomic fiber proximate to the pulmonary artery toaffect one or more of cardiac output and hemodynamics; and a frameconnected to the distal ends of the plurality of insulated electricalconductors at a plurality of coupling points, the frame changeablebetween a first collapsed configuration in a catheter lumen and a secondexpanded configuration out of the catheter lumen, the plurality ofelectrodes proximal to the coupling points.
 15. The device of claim 14,further comprising: a controller in electrical communication with theplurality of electrodes; and a sensor configured to measure a biologicalparameter and to generate sensor signals receivable by the controller.16. The device of claim 15, wherein the biological parameter comprisesone or more of arterial blood pressure, central venous pressure,capillary pressure, systolic pressure variation, arterial blood gases,cardiac output, systemic vascular resistance, pulmonary artery wedgepressure, and mixed venous oxygen saturation.
 17. The device of claim16, wherein the controller is configured to adjust the therapy signaldelivered by the therapy delivery device in response to the sensorsignals.
 18. The device of claim 14, wherein the plurality of electrodesis spaced from a proximal end of the frame by segments of the pluralityof insulated electrical conductors.
 19. The device of claim 14, whereinthe plurality of electrodes is proximate to a proximal end of the frame.20. The device of claim 14, wherein each of the plurality of electrodesis annularly disposed on one of the plurality of insulated electricalconductors.